This study examines the possible relationship existing between the HLA-DR gene and attention deficit hyperactivity disorder (ADHD) and/or mental retardation (MR). The diagnosis of ADHD and mental retardation were established through clinical interviews with the parents, children and teachers, according to the criteria in DSM-IV. HLA-DRB1 genotyping was performed both by polymerase chain reaction-sequence specific primers (PCR-SSP) and by sequence based typing (SBT) in a cohort of 81 affected children and a sample of 100 healthy controls. Here, we report a positive association of HLA-DR4 with ADHD but not with MR. The study adds confirmation to the role of the HLA-DRB1 in the etiology of some types of childhood neuropsychiatric illnesses.